Numerous pathologies comprising an auto-immune reaction and inflammatory diseases have an uncertain or unknown etiology and may have a multifactor origin.
Apparently, a disorder or a stimulation of the immune system of patients constitutes an important element of the progression of those diseases or pathologies.
Among the auto-immune diseases, systemic lupus erythematosus disease (SLE) is characterized by numerous biological and clinical signs.
However, SLE is a pathology with several clinical signs which may evolve and/or recover themselves each other (i.e. renal, cardiac, brain damages, . . . ). Therefore, as it exists non common and constant signs for all the patients affected by SLE, it has been proposed that the "diagnostic" of this pathology is now obtained from simultaneous characterization of at least four clinical and/or biological signs related to SLE (Arthritis and Rheumatism, Vol. 25, No 11 (1982), Official Journal of the American Rheumatism Association Section of the Arthritis Foundation).
The table 1 represents the sensitivity and the specificity of several preliminary criteria used for the diagnostic of systemic lupus erythematosus (serological and clinical tests).
TABLE 1 ______________________________________ Comparison of sensitivity and specificity of elements in the 1982 and 1971 patient database Sensitivity.sup.1 Specificity.sup.2 Element 1982 1971 1982 1971 ______________________________________ Malar rash 101/177 (57) (64) 156/162 (96) (98) Discoid rash 31/177 (18) (17) 161/162 (99) (99) Alopecia 99/177 (56) (43) 143/162 (88) (97) Photosensitivity 76/176 (43) (37) 155/162 (96) (99) Oral ulcers 47/177 (27) (15) 155/162 (96) (99) Raynaud's 51/176 (29) (20) 132/162 (81) (99) Arthritis 152/177 (86) (86) 60/162 (37) .sup. NA.sup.3 Proteinuria 89/177 (50) (61) 148/157 (94) (82) Urinary casts 64/176 (36) (48) 152/157 (97) (89) Dementia 11/177 (6) NA 160/162 (99) NA Seizures 21/177 (12) (13) 160/162 (99) (98) Coma 8/177 (5) NA 162/162 (100) NA Psychosis 22/176 (13) (19) 161/162 (99) (95) Focal neurologic 21/177 (12) (11) 155/161 (96) (92) Pleurisy 92/177 (52) (60) 144/162 (89) (91) Pericarditis 31/177 (18) (19) 155/162 (96) (97) Haemolytic anaemia 31/176 (18) (16) 160/161 (99) (98) Leucopenia 82/177 (46) (40) 144/161 (89) (94) Thrombocytopenia 37/177 (21) (11) 160/161 (99) (98) LE cells 58/79 (73) (92) 46/48 (96) (98) Sm antibody 34/108 (31) NA 59/62 (95) NA Serologic test for syphilis 19/129 (15) (12) 80/80 (100) (99) Renal biopsy 57/69 (83) NA 10/10 (100) NA Skin biopsy 47/69 (68) NA 13/16 (81) NA Antinuclear antibody 174/175 (99) NA 68/139 (49) NA DNA antibody 113/168 (67) NA 84/91 (92) NA CH50 84/120 (70) NA 33/47 (70) NA C3 88/137 (64) NA 69/76 (91) NA C4 65/102 (64) NA 33/51 (65) NA C2 0/0 NA 0/0 NA ______________________________________ .sup.1 : Sensitivity was determined on the SLE population and is expresse as the number of patients who were positive over the number of patients i whom the test was determined. Number in parenthesis indicates percentage. .sup.2 : Specificity was determined on the control population and is expressed as the number of patients who were negative or normal over the number of patients in whom the test was determined. .sup.3 : NA = data non available
State of the Art
However, in order to improve the diagnostic of said pathology, efforts have been made to develop specific and reliable detection devices on the basis of clinical biology analysis.
The presently used techniques are based on the detection in the serum of anti-nuclear antibodies (ANA) directed against the autologous components present in the cell nucleus. The presence of those anti-nuclear components is associated to clinical manifestations of some auto-immune diseases.
The detection of those antibodies is generally effected previously to other tests for confirming the existence of an auto-immune disease.
The anti-nuclear auto-antibodies (ANA) can be divided into two subgroups, the anti-DNA auto-antibodies and the anti-ENA auto-antibodies (extractable nuclear antigens).
A better characterization of those anti-nuclear auto-antibodies (ANA) would allow to obtain a more detailed diagnostic on the auto-immune disease type.
Moreover, it has been shown that sera of SLE-affected patients contain a mixture of antibodies respectively able to react not only with nuclear DNA, but also with RNA and nucleoproteins. Besides, some patients presenting clinical signs of Systemic lupus erythematosus (SLE) have no significiant titers of anti-DNA antibodies.
Consequently, it has not been shown yet that the presence of such antibodies in patients can be considered as a characteristic SLE marker.
In the European Patent EP-0252787 granted to Institut Pasteur and INSERM, a composition of isolated and purified cell surface polypeptides and the application thereof for detecting SLE are described. These purified polypeptides are characterised by a molecular weight less than 60 KD (55 KD, 43 KD, 34 KD, 33 KD, 17 KD, 16 KD and 14 KD).
However, for the inflammatory diseases and the pathologies comprising an auto-immune reaction, particularly for SLE, it has not been yet possible to provide a sufficiently specific antigenic structure to obtain a reliable diagnostic (in specificity and in sensitivity) for those pathologies and diseases.
Aims of the Invention
The present invention aims to provide a marker and a diagnostic device allowing to improve the diagnostic for inflammatory diseases and/or pathologies comprising an auto-immune reaction, particularly for SLE and/or Sjogren Syndrom.
A further aim is to provide a marker which improves the specificity and sensibility of SLE diagnostic, preferably an early diagnostic of SLE.
Another aim of the invention is to provide a method to obtain the marker, particularly a nucleic acid according to the invention.
A further aim of the invention is to provide an easy and reproducible method to obtain said marker in high amounts.